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Background: Understanding biochemical and structural changes of the extracellular matrix in Achilles tendinosis might be important for developing mechanism-based therapies.
Hypothesis: In Achilles tendinosis, changes occur in biochemical composition and collagen turnover rate.
Study Design: Descriptive laboratory study.
Methods: From 10 patients undergoing surgery for Achilles tendinopathy, 1 tendinosis biopsy specimen and 1 biopsy specimen of macroscopically healthy tendon tissue adjacent to the lesion were collected. Furthermore, biopsy samples were collected from 3 donors with asymptomatic Achilles tendons. Water content, collagen content, percentage of denatured collagen, amount of lysine hydroxylation, number of enzymatic and nonenzymatic crosslinks, matrix metalloproteinase activity, and matrix metalloproteinase and collagen gene-expression levels were analyzed.
Results: In tendinotic lesions, the water content was highest, and collagen content was subnormal with higher amounts of denatured/damaged collagen. Low pentosidine levels in tendinotic tissue indicated the presence of relatively young collagenous matrix. More hydroxylated lysine residues were present in tendinotic samples, but enzymatic crosslinks revealed no differences between tendinotic, adjacent, and healthy samples. In tendinotic specimens, matrix metalloproteinase activity was higher, matrix metalloproteinase gene-expression profile was altered, and collagen type I and III gene expression were upregulated.
Conclusion: In Achilles tendinosis, the collagen turnover rate is increased, and the natural biochemical composition of the collagenous matrix is compromised.
Clinical Relevance: Although tendon tissue directly adjacent to an Achilles tendinosis lesion looks macroscopically healthy, histological and biochemical degenerative changes in adjacent tissue are evident, which may have implications for surgical interventions.
Press Release: Scientists discover new clues explaining tendon injury
Tendon disorders cost the UK economy more than £7bn a year and now scientists at Queen Mary, University of London have identified a vital component of tendons which could help treat them.
The research, published in the highly regarded Royal Society journal Interface today (4 July), found that a component of tendons known as the interfascicular matrix (IFM) is essential for their function.
“Tendon disorders are highly debilitating and painful, and may herald the end of an Olympic athlete’s career,” said co-author Dr Hazel Screen, a senior lecturer in medical engineering at Queen Mary, University of London.
“Even today, with advancements in sports science, little is known about tendon health management, and we still do not understand why some people are more prone to tendon injury than others.
However, we have now found that the matrix which binds the fascicles together in the tendon, the IFM, is essential for tendon function and that changes to this structure may be responsible for tendon injury.”
Scientists at Queen Mary, along with colleagues from University of Liverpool and University College London, are working on a project funded by the Horserace Betting Levy Board, in which they have been dissecting tendons from horses in order to better understand the role of the IFM.
Tendon injury is common in horses as well as humans, with an economic impact of more than £3bn a year in horse racing. Around 16,000 horses are in training each year and the tendon injury rate is as high as 43% with few horses returning to racing after injury.
Lead author Dr Chavaunne Thorpe from the School of Engineering and Materials Science at Queen Mary, University of London explained: “A specific tendon in horses known as the superficial digital flexor tendon (SDFT) stretches and recoils in the same way as the Achilles tendon and is injured in the same way.
“We tested how the components within the SDFT worked to enable the tendon to stretch and function effectively.
“When we looked at its capacity to stretch, we found that the IFM, previously thought to be unimportant in tendon function, was essential to SDFT extension in horses. We found that tendons with a stiffer IFM were not able to stretch as far before they failed.”
The finding suggests that the IFM may be critical in preventing tendon overuse injury, and the authors are now trying to find out exactly how this is achieved.
Dr Screen added: “If we are able to manipulate the IFM, we could potentially design a diagnostic test to see whether someone is more susceptible to tendon injury than others, and also pave the way for prospective treatments.”
The objective of this study was to investigate the fibrocartilaginous differentiation occurring in midportion Achilles tendinopathy.
Tendon samples were retrospectively collected from 23 patients, who had undergone surgery for midportion Achilles tendinopathy resistant to conservative treatment. Based on histological scores, the biopts were subdivided into three categories: a light, moderate and severe histopathological stage. Throughout these stages, immunohistochemical staining was performed against biglycan, aggrecan and collagen type II, components characteristic for fibrocartilage. Staining of these components was evaluated using a semi-quantitative scoring method.
The immunohistochemical scores of biglycan and aggrecan were statistically significant between the histopathological stages (P < 0.001). The immunohistochemical scores were positively correlated with the increasing histopathological stages [Spearman’s correlation coefficient = 0.93 for biglycan and 0.78 for aggrecan (P < 0.001)]. Staining for collagen type II remained negative throughout these stages.
Immunohistochemical staining of the fibrocartilaginous components biglycan and aggrecan showed a progressive increase, correlated with a further evolved histopathological stage. This observation gave arguments for an increased differentiation towards fibrocartilaginous components at protein level in midportion Achilles tendinopathy.
Neovascularization is frequently observed in tendinopathy. Previous studies have focused on the role of neovascularization in Achilles tendinopathy, but have been conducted in small series. It is still unclear whether the degree of neovascularization is related to severity of symptoms. The purpose was to study the relationship between ultrasonographic neovascularization and clinical severity in patients with Achilles tendinopathy. In this prospective cohort study, data on 127 patients (141 tendons) were assembled from databases of three clinical trials. All patients followed an eccentric exercise program. The Öhberg neovascularization score (0–4+) and Victorian Institute of Sports Assessment-Achilles (VISA-A) score (split into domains: pain, function and activity) were collected during baseline and follow-up. The relationship between neovascularization and VISA-A score was calculated. At baseline, 107 tendons (76%) showed some degree of neovascularization. In 556 coupled measurements, neovascularization was weakly related to the VISA-A score [Exp (B) 1.017, 95% confidence interval (CI), 1.007–1.026]. No significant relationship was found between neovascularization and the pain domain (P = 0.277) and the activity domain (P = 0.283), but there was between neovascularization and the function domain of the VISA-A score [Exp (B) = 1.067, 95% CI 1.018–1.119]. In conclusion, neovascularization in Achilles tendinopathy is weakly related to clinical severity, mainly based on the function domain of the VISA-A score.